(Adapted from the Investigator~s Abstract): To prolong the life of wood used in the construction industry, toxic chemical have been used since the 1930's to impregnate and protect the wood. These chemicals have been highly successful in protecting wood against termites, other insects, fungus, and rot. Nearly 300 million cubic feet of pressure- treated wood are reduced and used each year. The most common chemical treatment is the impregnation of the wood with chromated copper arsenate (CCA). Although these metals possess a wide range of toxic properties, the U.S. EPA ruled in 1984 that CCA pressure- treated wood is safe for interior use, play structures, garden edging, and vegetable stakes. This ruling was based on the tight,'irreversible' binding of the metals to the wood fibers as reported by the trade association of pressure-treated wood manufacturers. Although small amounts of the metals are extracted in aqueous solutions common to fresh and salt water environments, no research efforts has examined the bio-availability of these metals upon inhalation of the airborne wood particles generated at construction sites. This research proposal will examine the bioavailability of these metals after the CCA wood encounters, and is processed by, phagocytic cells. The hypothesis is that the hostile intracellular environment of phagocytic cells (e.g., vacuoles containing proteolytic enzymes and increased acidity) will release the toxic metals bound to the wood fibers. This hypothesis will be examined by studying the ability of pressure-treated wood dust to induce: 1) cytotoxicity in arsenic-sensitive cells (arsenic bio- availability); 2) metallothionein (arsenic and copper bio-availability); and 3) DNA-protein crosslinks (chromium bio-availability) in phagocytic cells. Observation of positive findings in the these endpoints would provide direct evidence that the intracellular environment of phagocytic cell is able to reverse the ~irreversible~ nature of the heavy metal binding to wood fibers and thus, suggest that inhalation of pressure-treated wood dust poses an occupational hazard.